Last year we reported the development of a sensitive HPLC assay for imipramine and its metabolites. With this method we have studied the kinetics of imipramine metabolism in isolated rat liver hepatocytes and compared the results to those obtained in rat liver microsomes and in vivo. The results indicate that while isolated rat liver hepatocytes offer a better in vitro model of imipramine metabolism than do rat liver microsomes, they do not completely mimic the in vivo situation.